We plan to examine the Na and Ca currents in single cardiac muscle cells. For the Na current emphasis will be placed upon the time constant, tau, for recovery from inactivation and the effect of antiarrhythmic agents on it, the relationship between INa and dV/dt max, and certain channel characteristics such as selectivity, voltage-dependence of TTX blockage and unit conduction. For the Ca current, emphasis will be given to the shape of the power density spectrum (which will point to a channel or carrier mechanism), the unusual voltage dependence of tau inactivation, selectivity and mechanism of action of NE and ACh. A pair of unusual approaches have been combined to allow satisfactory voltage clamp and internal perfusion of single cardiac myocytes. Individual heart muscle cells are dispersed by perfusion and enzymatic treatment; the dispersed cells are harvested and single myocytes are examined using a suction pipette which provides methods of voltage clamp and internal perfusion. The advantages of the method are better spatial control of voltage, satisfactory temporal resolution and access to the cell's intracellular ionic constituents. Ionic currents are separated by ion substitution and/or specific pharmacological blockers. Successful experiments have already been reported (Nature, 1979). Part of the proposal deals with evaluating this new approach both with respect to its limitations and its optimization.